A Genetically Retargeted Adenoviral Vector Enhances Viral Transduction in Esophageal Carcinoma Cell Lines and Primary Cultured Esophageal Resection Specimens

Christianne J. Buskens, Willem A. Marsman, John G. Wesseling, G. Johan A Offerhaus, Masato Yamamoto, David T. Curiel, Piter J. Bosma, J. Jan B Van Lanschot, J. R. Izbicki, M. Reed, P. A. Clavien

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells. Summary Background Data: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an arginine-glycine-aspartate (RGD) tripeptide in the fiber knob, might overcome this problem. Methods: Four esophageal carcinoma cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency. Results: In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of carcinoma cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces tumor cells more efficiently than normal cells. Conclusions: This study demonstrates that an RGD retargeted adenovirus infects human esophageal carcinoma cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for cancer gene therapy so far.

Original languageEnglish (US)
Pages (from-to)815-826
Number of pages12
JournalAnnals of Surgery
Volume238
Issue number6
StatePublished - Dec 2003
Externally publishedYes

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Carcinoma
Cell Line
Adenoviridae
Genetic Therapy
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Genes
Human Adenoviruses
Oncogenic Viruses
Primary Cell Culture
Neoplasm Genes
Green Fluorescent Proteins
Luciferases
Reporter Genes
Integrins
Glycine
Neoplasms

ASJC Scopus subject areas

  • Surgery

Cite this

Buskens, C. J., Marsman, W. A., Wesseling, J. G., Offerhaus, G. J. A., Yamamoto, M., Curiel, D. T., ... Clavien, P. A. (2003). A Genetically Retargeted Adenoviral Vector Enhances Viral Transduction in Esophageal Carcinoma Cell Lines and Primary Cultured Esophageal Resection Specimens. Annals of Surgery, 238(6), 815-826.

A Genetically Retargeted Adenoviral Vector Enhances Viral Transduction in Esophageal Carcinoma Cell Lines and Primary Cultured Esophageal Resection Specimens. / Buskens, Christianne J.; Marsman, Willem A.; Wesseling, John G.; Offerhaus, G. Johan A; Yamamoto, Masato; Curiel, David T.; Bosma, Piter J.; Van Lanschot, J. Jan B; Izbicki, J. R.; Reed, M.; Clavien, P. A.

In: Annals of Surgery, Vol. 238, No. 6, 12.2003, p. 815-826.

Research output: Contribution to journalArticle

Buskens, CJ, Marsman, WA, Wesseling, JG, Offerhaus, GJA, Yamamoto, M, Curiel, DT, Bosma, PJ, Van Lanschot, JJB, Izbicki, JR, Reed, M & Clavien, PA 2003, 'A Genetically Retargeted Adenoviral Vector Enhances Viral Transduction in Esophageal Carcinoma Cell Lines and Primary Cultured Esophageal Resection Specimens', Annals of Surgery, vol. 238, no. 6, pp. 815-826.
Buskens, Christianne J. ; Marsman, Willem A. ; Wesseling, John G. ; Offerhaus, G. Johan A ; Yamamoto, Masato ; Curiel, David T. ; Bosma, Piter J. ; Van Lanschot, J. Jan B ; Izbicki, J. R. ; Reed, M. ; Clavien, P. A. / A Genetically Retargeted Adenoviral Vector Enhances Viral Transduction in Esophageal Carcinoma Cell Lines and Primary Cultured Esophageal Resection Specimens. In: Annals of Surgery. 2003 ; Vol. 238, No. 6. pp. 815-826.
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abstract = "Objective: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells. Summary Background Data: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an arginine-glycine-aspartate (RGD) tripeptide in the fiber knob, might overcome this problem. Methods: Four esophageal carcinoma cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency. Results: In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of carcinoma cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces tumor cells more efficiently than normal cells. Conclusions: This study demonstrates that an RGD retargeted adenovirus infects human esophageal carcinoma cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for cancer gene therapy so far.",
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AU - Buskens, Christianne J.

AU - Marsman, Willem A.

AU - Wesseling, John G.

AU - Offerhaus, G. Johan A

AU - Yamamoto, Masato

AU - Curiel, David T.

AU - Bosma, Piter J.

AU - Van Lanschot, J. Jan B

AU - Izbicki, J. R.

AU - Reed, M.

AU - Clavien, P. A.

PY - 2003/12

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N2 - Objective: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells. Summary Background Data: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an arginine-glycine-aspartate (RGD) tripeptide in the fiber knob, might overcome this problem. Methods: Four esophageal carcinoma cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency. Results: In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of carcinoma cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces tumor cells more efficiently than normal cells. Conclusions: This study demonstrates that an RGD retargeted adenovirus infects human esophageal carcinoma cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for cancer gene therapy so far.

AB - Objective: To evaluate if an integrin-retargeted adenoviral vector could establish a more efficient and tumor-specific gene transfer in esophageal carcinoma cells. Summary Background Data: Although preclinical data indicated that adenoviral gene therapy could be a promising novel treatment modality for various malignancies, clinical results are often disappointing. An important problem is the decreased tumoral expression of the Coxsackie and adenovirus receptor (CAR), which mediates adenoviral entry. Retargeting the adenoviral vector to other cellular receptors, by inserting an arginine-glycine-aspartate (RGD) tripeptide in the fiber knob, might overcome this problem. Methods: Four esophageal carcinoma cell lines and 10 fresh surgical resection specimens were cultured. All were infected with the native adenovirus (Ad) and the retargeted adenovirus (AdRGD), encoding for the reporter genes luciferase or Green Fluorescent Protein to analyze gene transfer efficiency. Results: In all cell lines, an increase in viral expression per cell and an increase in the percentage of transduced cells were seen with the retargeted adenovirus. Also, in the primary cultures of carcinoma cells, a more efficient gene transfer was seen when the retargeted vector was used. This phenomenon was less pronounced in normal cells, indicating that the RGD virus transduces tumor cells more efficiently than normal cells. Conclusions: This study demonstrates that an RGD retargeted adenovirus infects human esophageal carcinoma cells with enhanced efficiency, while in normal esophageal cells this effect is less pronounced. Therefore, this retargeted vector is expected to have a better performance in vivo, when compared with nonretargeted vectors used for cancer gene therapy so far.

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